Cystic Fibrosis (CF) is a debilitating and ultimately fatal genetic disorder, caused by the failure of a chloride channel, the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), to reach its proper place on the cell surface, where it transports chloride ions and water into and out of the cell. CF causes the lungs and gastrointestinal tract to become clogged with thick mucous secretions and leads to bacterial infections, failure to thrive, and eventually to respiratory failure, with a life expectancy of about 30 years.
The most common form of CF is caused by the mutation Delta-F508, which produces an active, but mis-folded CFTR protein. Nearly 90% of people with CF carry at least one copy of the Delta-F508 CFTR gene.
Research led by Yale professors Michael Caplan, M.D. and Marie Egan, M.D. and their collaborator in Toronto, Gergely Lukacs, M.D..studied compounds that alter or compensate for the defect on Delta-F508.
They found that the Delta-F508 defect is corrected in tissue culture and in mouse model systems by curcumin, the component that gives the spice turmeric its bright yellow color. In cultured cells, the CFTR protein moved to the surface of the cells, and in CFTR mice, the nasal and rectal epithtlia regained nearly normal function.
"While these data are very encouraging, it is much too early to say whether curcumin will offer an effective treatment for most people with CF," said Caplan, professor of cellular and molecular physiology. He noted that curcumin was not expected to be effective for some of the other CFTR mutations.
Curcumin is non-toxic to humans and clinical trials for safety and effective dosing are beginning with Seer Pharmaceutical and Cystic Fibrosis Foundation Therapeutics, an affiliate of the Cystic Fibrosis Foundation.
This research was funded by grants from the Alyward Family/PitneyBowes Gift Fund, Seer Pharmaceuticals, the Cystic Fibrosis Foundation, the NIH, and the CIHR.
CITATION: Science 304: 600- 602 (April 23, 2004).